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15 June 2006

Volume 193, Number 12
The Journal of Infectious Diseases 2006;193:1658–1665
This article is in the public domain, and no copyright is claimed.
0022-1899/2006/19312-0008
DOI: 10.1086/503372
MAJOR ARTICLE

Protection of Rhesus Monkeys against Dengue Virus Challenge after Tetravalent Live Attenuated Dengue Virus Vaccination

Wellington Sun,1

Ananda Nisalak,3

Montip Gettayacamin,4

Kenneth H. Eckels,2

J. Robert Putnak,1

David W. Vaughn,1,a

Bruce L. Innis,1,a

Stephen J. Thomas,1 and

Timothy P. Endy3,a

Departments of 1Virus Diseases and 2Biologics Research, Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland; Departments of 3Virology and 4Veterinary Medicine, United States Army Medical Component, Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand

Rhesus monkeys develop viremia after dengue virus (DENV) inoculation and have been used as an animal model to study DENV infection and DENV vaccine candidates. We evaluated, in this model, the protective efficacy of a live attenuated tetravalent DENV vaccine (TDV) candidate against parenteral challenge with parental near‐wild‐type DENV strains. Twenty monkeys were vaccinated with TDV at 0 and 1 month, and 20 unvaccinated monkeys served as controls. Vaccinated animals and their controls were inoculated with 103–104 pfu of challenge virus 4.5 months after the second vaccination. Primary vaccination resulted in 95%, 100%, 70%, and 15% seroconversion to DENV serotypes 1, 2, 3, and 4 (DENV‐1, ‐2, ‐3, and ‐4), respectively. After the second vaccination, the seropositivity rates were 100%, 100%, 90%, and 70%, respectively. Vaccination with TDV resulted in complete protection against viremia from DENV‐2 challenge and in 80%, 80%, and 50% protection against challenge with DENV‐1, ‐3, and ‐4, respectively. Our results suggest that the TDV can elicit protective immunity against all 4 DENV serotypes. Interference among the 4 vaccine viruses may have resulted in decreased antibody responses to DENV‐3 and ‐4, which would require reformulation or dose optimization to minimize this interference during testing of the vaccine in humans.

Received 30 September 2005; accepted 17 November 2005; electronically published 9 May 2006.

Reprints or correspondence: Dr. Wellington Sun, Dept. of Virus Diseases, Div. of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, 503 Robert Grant Ave., Silver Spring, MD 20910‐7500 ().

Cited by

Jorge Martín, Lisset Hermida, Jorge Castro, Laura Lazo, Rafael Martínez, Lázaro Gil, Yaremis Romero, Pedro Puente, Santiago Zaragoza, Karelia Cosme, María G. Guzmán, Jane Cardosa, Gerardo Guillén. (2009) Viremia and antibody response in green monkeys ( Chlorocebus aethiops sabaeus ) infected with dengue virus type 2: A potential model for vaccine testing. Microbiology and Immunology 53:4, 216-223
Online publication date: 1-May-2009.
CrossRef
Julian W. Tang, Muhammad R. Khanani, Adnan M. Zubairi, Wai Y. Lam, Florence Lai, Khursheed Hashmi, Arif Hussain, Saba Jamal, Paul K.S. Chan. (2009) A wide spectrum of dengue IgM and PCR positivity post-onset of illness found in a large dengue 3 outbreak in Pakistan. Journal of Medical Virology 80:12, 2113-2121
Online publication date: 1-Jan-2009.
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M. Shannon Keckler, Vida L. Hodara, Laura M. Parodi, Luis D. Giavedoni. (2008) Novel Application of Nonhuman Primate Tethering System for Evaluation of Acute Phase SIVmac251 Infection in Rhesus Macaques (Macaca mulatta). Viral Immunology 20:4, 623-634
Online publication date: 1-Jan-2008.
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Stephen S. Whitehead, Joseph E. Blaney, Anna P. Durbin, Brian R. Murphy. (2007) Prospects for a dengue virus vaccine. Nature Reviews Microbiology 5:7, 518-528
Online publication date: 1-Aug-2007.
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  • Potential conflicts of interest: Partially on the basis of this study, some authors were named inventors on an awarded patent (6638514), titled “Multivalent dengue vaccine,” filed 24 March 2000 and awarded 28 October 2003.

    Financial support: US Army Medical Research and Materiel Command.

    The views expressed herein are those of the authors and do not necessarily represent those of the Department of the Army or Department of Defense.

  • Present affiliations: Military Infectious Diseases Research Program, Medical Research and Materiel Command, Fort Detrick (D.W.V.), and Division of Communicable Diseases and Immunology, Walter Reed Army Institute of Research, Silver Spring, Maryland (T.P.E.); GlaxoSmithKline, King of Prussia, Pennsylvania (B.L.I.).

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